Implementation of a Cardiogenic Shock Team in a Tertiary Academic Centre.

BACKGROUND: Observational studies have shown that the management of patients with cardiogenic shock (CS) by dedicated multidisciplinary teams improve clinical outcomes. Nevertheless, these studies reflect a specific organisational setting with most patients being transfers from referring hospitals, hospitalised in cardiac intensive care units (ICU), or treated with mechanical circulatory support (MCS) devices. The purpose of this study was to document the organisation and outcomes of a CS team offering acute care in all-comer population. METHODS: A CS team was developed in a large academic tertiary institution. The team consisted of emergency care physicians, critical care cardiologists, interventional cardiologists, cardiac surgeons, ICU physicians and heart failure specialists and was supported by predefined operating protocol, dedicated communication platform and regular team meetings. RESULTS: Over 12 months, 70 CS patients (69±13 years old, 67% males) were included. Acute myocardial infarction (AMI-CS) was the most common cause (64%); 31% of the patients presented post-resuscitated cardiac arrest and 56% needed invasive mechanical ventilation (IMV). Coronary angiography was performed in 70% and 53% had percutaneous coronary intervention. MCS was used in 10% and 6% were referred for urgent cardiac surgery. The in-hospital mortality in our centre was 40% with 39% of the patients dying within 24-hours from presentation. 76% of the alive patients were discharged home. CONCLUSIONS: Across an all-comer population, AMI was the most common cause of CS. A significant number of patients presented post cardiac arrest, and the majority required IMV. Mortality was high with a significant number dying within hours of presentation.

Treatment Strategies and Outcomes of Right Ventricular Failure Post Left Ventricular Assist Device Implantation: An INTERMACS Analysis.

Right heart failure (RHF) management after left ventricular assist device (LVAD) implantation includes inotropes, right ventricular mechanical support, and heart transplantation. The purpose of this study is to compare different RHF treatment strategies in patients with a magnetically levitated centrifugal LVAD. A total of 6,632 Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) patients from 2013 to 2020 were included. Of which, 769 (69.6%) patients (group 1) were supported with inotropes (≥14 days post-LVAD implantation), 233 (21.1%) patients (group 2) were supported with temporary right ventricular assist device (RVAD) that was implanted during LVAD implant, 77 (7.0%) patients (group 3) with durable centrifugal RVAD implanted during the LVAD implant, and 26 (2.4%) patients (group 4) were supported with RVAD (temporary or permanent), which was implanted at a later stage. Groups 1 and 4 had higher survival rates in comparison with group 2 (hazard ratio [HR] = 0.513, 95% confidence intervals [CIs] = 0.402-0.655, p < 0.001, versus group 1) and group 3 (HR = 0.461, 95% CIs = 0.320-0.666, p < 0.001, versus group 1). Patients in group 3 showed higher heart transplantation rates at 12 and 36 months as compared with group 1 (40.4% and 46.6% vs. 21.9% and 37.4%, respectively), group 2 (40.4% and 46.6% vs. 25.8% and 39.3%, respectively), and group 4 (40.4% and 46.6% vs. 3.8% and 12.0%, respectively). Severe RHF post-LVAD is associated with poor survival. Patients with LVAD who during the perioperative period are in need of right ventricular temporary or durable mechanical circulatory support constitute a group at particular risk. Improvement of devices tailored for right ventricular support is mandatory for further evolution of the field.

Differential Expression of Circulating Damage-Associated Molecular Patterns in Patients with Coronary Artery Ectasia.

Coronary artery ectasia (CAE) is defined as abnormal dilation of a coronary artery with a diameter exceeding that of adjacent normal arterial segment by >1.5 times. CAE is a pathological entity of the coronary arteries and characterized as a variant of coronary atherosclerosis. CAE frequently coexists with coronary artery disease (CAD). While inflammation appears to be involved, the pathophysiology of CAE remains unclear. Damage-associated molecular patterns (DAMPs), defined as endogenous molecules released from stressed or damaged tissue, are deemed as alarm signals by the innate immune system. Inflammatory agents can generate DAMPs and DAMPs can create a pro-inflammatory state. In a prospective cross-sectional study, we enrolled 29 patients with CAE and non-obstructive CAD, 19 patients with obstructive CAD without CAE, and 14 control subjects with normal (control) coronary arteries age- and sex-matched with the CAE patients, to investigate the differential expression of plasma DAMPs. Patients with CAE and non-obstructive CAD had increased plasma levels of the DAMPs S100B, S100A12, HMGB1, and HSP70, the DAMPs receptor TLR4, and miR328a-3p compared to CAD and controls. Plasma levels of the mir328a-3p target the protective soluble form of the DAMPs receptor for advanced glycation end products (sRAGE), and the antioxidant DJ-1 was decreased in both CAE and CAD compared to controls. In an in vitro human umbilical vein endothelial cells model, circulating levels of S100B, HMGB1, HSP70 as well as CAE patient plasma induced inflammatory responses. The differential expression of the DAMPs S100B, HSP70, HMGB1, and their receptors TLR4 and sRAGE in CAE versus CAD makes them attractive novel biomarkers as therapeutic targets and therapeutics.

Prediction of Long-Term Survival after Coronary Artery Bypass with Bilateral Internal Thoracic Artery Grafting: External Validation of A Contemporary Nomogram.

Background: This study aimed to verify the external validation of a contemporary nomogram in predicting long-term survival after an isolated coronary artery bypass with bilateral internal thoracic artery grafting (CABG-BITA). Methods: Consecutive patients who underwent CABG-BITA at a single center were included in the study. All the predictors of the original risk score (age, diabetes mellitus, chronic obstructive pulmonary disease, congestive heart failure, chronic renal failure, old myocardial infarction, ejection fraction, intra-aortic balloon pump and peripheral arterial disease) were available for analysis. Results: Among the 2846 consecutive patients, a total of 1176 (41.3%) deaths were recorded during the 31,383 patient years of follow-up. The median EuroSCORE II was 2.35, and the median follow-up was 11.1 years. The risk score showed 72.7% overall discriminatory ability as measured by Harrell's concordance statistic. It showed satisfactory calibration at 10, 15 and 20 years of follow-up. The risk score showed a time-varying nonlinear effect, and accordingly, adjusted long-term survival predictions were calculated. There were subgroups (scores < 50 points) with favorable 20-year survival rates ranging from 77% to 60%. Higher risk subgroups (scores > 90 points) showed poor 20-year survival rates ranging from 22% to 4%. Conclusions: The validated risk score represents a useful algorithm for the detection of patients who could benefit after CABG-BITA with respect to long-term survival. Although further multi-center studies are required worldwide to reveal the usefulness of this score in the clinical setting, its wide adoption may act as a motivation for cardiac surgeons resulting in higher numbers of CABG-BITA procedures.

Superiority of bilateral internal thoracic artery grafting in long-term survival after coronary artery bypass through the lenses of a bedside risk score.

OBJECTIVE: Risk algorithms for the prediction of long-term survival after coronary artery bypass grafting (CABG) do not include the use of bilateral internal thoracic artery (BITA) grafting among the independent predictors. We sought to reveal the superiority of BITA grafting in the long-term outcome through the lenses of an existing bedside risk score (BRS). METHODS: This study analyzed data from 5,666 consecutive patients undergoing isolated (n = 4,715 - BITA = 2,792) and combined (n = 951 - BITA = 246) CABG. The mean follow-up period was 10.3 years (interquartile range, 9.9 years). All the predictors of an existing BRS were available for analysis (age, body mass index, ejection fraction, unstable hemodynamic state, left main disease, cerebrovascular disease, peripheral arterial disease, congestive heart failure, malignant ventricular arrhythmia, chronic obstructive pulmonary disease, diabetes, and previous heart surgery). Furthermore, a modified BRS was constructed taking into account the use of BITA grafting and combined CABG. RESULTS: The good discriminatory ability and satisfactory calibration of the BRS was confirmed in the isolated CABG subgroup. The modified BRS showed improved discriminatory ability and similar calibration. It showed a time-varying coefficient, and accordingly, we calculated the adjusted survival predictions up to 20 years after isolated and combined CABG with or without BITA grafting. Patients with BITA grafting in the low-risk quartile showed 68.4% and 65.5% predicted survival rates at 20 years in the isolated and combined CABG subgroups, respectively, versus the survival rates of 56.4% and 52.8% observed among patients without BITA grafting. CONCLUSION: The modified BRS is a useful simplified algorithm for clinicians in choosing treatment intervention for severe isolated or combined coronary artery disease. We clearly demonstrated the superiority of BITA grafting in long-term survival throughout the entire range of the modified BRS.

Cytoprotective Mechanisms of DJ-1: Implications in Cardiac Pathophysiology.

DJ-1 was originally identified as an oncogene product while mutations of the gene encoding DJ-1/PARK7 were later associated with a recessive form of Parkinson's disease. Its ubiquitous expression and diversity of function suggest that DJ-1 is also involved in mechanisms outside the central nervous system. In the last decade, the contribution of DJ-1 to the protection from ischemia-reperfusion injury has been recognized and its involvement in the pathophysiology of cardiovascular disease is attracting increasing attention. This review describes the current and gaps in our knowledge of DJ-1, focusing on its role in regulating cardiovascular function. In parallel, we present original data showing an association between increased DJ-1 expression and antiapoptotic and anti-inflammatory markers following cardiac and vascular surgical procedures. Future studies should address DJ-1's role as a plausible novel therapeutic target for cardiovascular disease.

Increased right atrial appendage apoptosis is associated with differential regulation of candidate MicroRNAs 1 and 133A in patients who developed atrial fibrillation after cardiac surgery.

Atrial fibrillation (AF) following on-pump coronary artery bypass grafting (CABG) is a common condition associated with increased morbidity and mortality. We investigated the possibility that miRs may play a contributory role in postoperative AF and associated apoptosis. A total of 42 patients (31 males and 11 females, mean age 65.0 ±â€¯1.3 years) with sinus rhythm and without a history of AF were prospectively enrolled. We examined the levels of the muscle-specific miRs 1 and 133A and markers of apoptosis including TUNEL staining, caspase-3 activation, Bcl2 and Bax mRNAs in right atrial appendage (RAA) biopsies and blood plasma taken before aortic cross-clamping and after reperfusion. After reperfusion, indices of apoptosis increased the RAA. There was no change in tissue or plasma miR -1 and -133A levels compared to pre CABG. However, in patients who postoperatively developed AF (n = 14, 7 males and 7 females), compared to patients that remained in SR (n = 28, 24 males and 4 females) post CABG, tissue miR-1 increased whereas miR-133A decreased and negatively correlated with RAA apoptosis. Mechanistically, overexpression of miR-133A inhibited hypoxia-induced rat neonatal cardiomyocyte apoptosis and phosphorylated pro-survival Akt, responses abolished by a miR-133A antisense inhibitor oligonucleotide or by pre-treatment with an Akt inhibitor. In postoperative AF, differential regulation of pro- and anti-apoptotic miRs-1 and -133A respectively in the RAA, may contribute to postoperative apoptosis. These results provide new insights into molecular mechanisms of postoperative AF with potential therapeutic implications.

Lazaroid (U-74389G) ameliorates lung injury due to lipid peroxidation and nitric oxide synthase-dependent reactive oxygen species generation caused by remote systematic ischemia-reperfusion following thoracoabdominal aortic occlusion.

INTRODUCTION: Lung ischemia-reperfusion injury after thoracoabdominal aortic occlusion represents a major complication, which increases morbidity and mortality. In the present study we hypothesized that lazaroid U-74389G intravenous administration protects from lung ischemia-reperfusion injury through lipid peroxidation inhibition. MATERIALS AND METHODS: A total of 24 pigs were randomized in three groups. Group I (n = 8) underwent sham operation, group II (n = 8) underwent thoracoabdominal aortic occlusion for 45min and received placebo and group III (n = 8) received 3 doses of lazaroid (3 mg/kg) 60 and 30min before thoracoabdominal aortic occlusion and at 30min during thoracoabdominal aortic occlusion (duration 45min). Aortic occlusion was performed with aortic balloon-catheters under fluoroscopic guidance. All animals were sacrificed at the 7 t h postoperative day and lung specimens were harvested for molecular analysis. RESULTS: mRNA levels of leukotrienes LB4 (LTB4R2), LC4 (LTC4S) and nitric oxide synthase (NOS) isoforms including iNOS, nNOS and eNOS were determined with real-time RT-qPCR. Nitric oxide can either induce (iNOS) or inhibit (nNOS and eNOS) lipid peroxidation based on its specific isoform origin. Group III showed significantly reduced mRNA levels of LTB4R2 (-63.7%), LTC4S (-35.9%) and iNOS (-60.2%) when compared with group II (P < 0.05, for all). The mRNA levels of nNOS was significantly increased (+37.4%), while eNOS was slightly increased (+2.1%) in group III when compared with group II (P < 0.05 and P = 0.467 respectively). CONCLUSION: Lazaroid U-74389G may represent an effective pharmacologic intervention in reducing lung ischemia-reperfusion injury following thoracoabdominal aortic occlusion.

Antiapoptotic Effect of ß1 Blockers in Ascending Thoracic Aortic Smooth Muscle Cells: The Role of HSP70 Expression.

Heat shock proteins (HSPs) play an important role in the cellular adaptation to stress, a requisite for cell survival. The aortic wall appears to be a target for increased expression of HSPs during surgical stress. We aimed to define the expression and function of aortic HSP70 in 31 patients with normal ascending thoracic aortic diameter who underwent aortic valve replacement due to aortic valve stenosis and in 35 patients with dilated ascending thoracic aorta who underwent replacement of an ascending thoracic aortic aneurysm. To elucidate responsible signaling mechanisms we used an in vitro model of rat hypoxic aortic vascular smooth muscle cell (AVSMC) cultures. We demonstrated an increase in AVSMC HSP70 and an attenuation of the apoptotic markers (TUNEL-positive nuclei, caspase-3 activity, Bax/Bcl2 ratio) in aortic wall tissue specimens from both aortic valve stenosis and ascending thoracic aortic aneurysm patients on ß1 blockade with metoprolol. In vitro, metoprolol treatment of hypoxic rat AVSMCs increased nitric oxide (NO) production, induced heat shock factor 1 transport to the nucleus, upregulated HSP70, decreased p53 phosphorylation and attenuated apoptosis. Blockade of NO production, resulted in decreased HSP70 and prevented the metoprolol-induced anti-apoptotic response of hypoxic AVSMCs. We demonstrate an anti-apoptotic effect of metoprolol dependent on NO-induced HSP70 expression, and thus augmentation of HSP70 expression should be considered as a therapeutic approach to limit apoptosis in the human ascending thoracic aorta of patients undergoing cardiac surgery.

Development of novel real-time RT-qPCR methodologies for quantification of the COL11A1 mRNA general and C transcripts and evaluation in non-small cell lung cancer specimens.

PURPOSE: The purpose of this study was the development of new quantitative methodologies for the general (total) COL11A1 gene and the C transcript (RT-qPCR methods for A and E transcripts have already been developed by our group previously), the quantification of all COL11A1 transcripts and the investigation for the first time of their potential association with histopathological prognostic factors in lung cancer. METHODS: Real-time RT-qPCR methodologies with dual hybridization probes were developed on the Light Cycler 1.5 platform (Roche,Germany). All COL11A1 transcripts were measured in 27 cDNA lung tissue specimens in a blinded fashion (8 control and 19 non-small cell lung cancer (NSCLC) tissues with known histopathological data). Statistical analysis was performed with the IBM SPSS program. RESULTS: The novel real-time RT-qPCR methodologies were appropriately validated. All 19 NSCLC samples were positive for the general COL11A1 transcript (range 11.2-1198.0 copies/µg total RNA, while 5 out of 8 control samples were negative: mean values were also statistically significantly different (p<0.001). In 4 tumor samples (21%), no specific COL11A1 transcript was detected. Transcript C was detected in only 3 tumor samples. Regarding transcripts A and E, 13 out of 19 tumor samples were positive for either one (68%) and 11 for both (58%). CONCLUSIONS: No other statistically significant association of the specific transcripts with histopathological data was observed, most probably due to the limited number of samples. As the number of general COL11A1 transcripts/µg exceeds the sum of A+E+C transcripts in all samples, there is opportunity for discovery and identification of other transcripts as well.

Impact of donor age on cardiac transplantation outcomes and on cardiac function.

OBJECTIVES: Although the impact of older donors on heart transplant outcomes has been previously published, the survival results are conflicting. We herein analyse the impact of older donors on transplant survival and myocardial function. METHODS: The records of the patients who underwent heart transplant at Baylor University Medical Center at Dallas from November 2012 until March 2015 were reviewed and the data were extracted. The heart recipients were divided into two groups based on donors age; 50 years of age was the division point. The two groups were compared with regard to the following transplant outcomes: in-hospital and 1-year survival, severe (3R) rejection, primary graft dysfunction, myocardial performance as reflected by the inotropic score, left ventricular ejection fraction, intensive care unit and overall length of stay. RESULTS: Anoxia was more common cause of death in younger donors (43.9%), whereas intracranial bleeding was more frequent in older donors (48.1%, P = 0.016). The in-hospital survival and 1-year survival were the same between the two groups. Additionally, cardiac transplantation from older donors was not associated with higher incidence of graft dysfunction, higher inotropic support score, longer intensive care unit and total hospital length of stay or more frequent severe rejection episodes. The left ventricular ejection fraction was similar between the two groups. CONCLUSIONS: Heart transplant from older donors is not associated with lower in-hospital and mid-term survival if donors are carefully selected; furthermore, the graft function is comparable. The use of hearts from donors older than 50 years of age can be expanded beyond critically ill recipients in carefully selected recipients.

Development of novel real-time PCR methodology for quantification of COL11A1 mRNA variants and evaluation in breast cancer tissue specimens.

BACKGROUND: Collagen XI is a key structural component of the extracellular matrix and consists of three alpha chains. One of these chains, the α1 (XI), is encoded by the COL11A1 gene and is transcribed to four different variants at least (A, B, C and E) that differ in the propensity to N-terminal domain proteolysis and potentially in the way the extracellular matrix is arranged. This could affect the ability of tumor cells to invade the remodeled stroma and metastasize. No study in the literature has so far investigated the expression of these four variants in breast cancer nor does a method for their accurate quantitative detection exist. METHODS: We developed a conventional PCR for the general detection of the general COL11A1 transcript and real-time qPCR methodologies with dual hybridization probes in the LightCycler platform for the quantitative determination of the variants. Data from 90 breast cancer tissues with known histopathological features were collected. RESULTS: The general COL11A1 transcript was detected in all samples. The developed methodologies for each variant were rapid as well as reproducible, sensitive and specific. Variant A was detected in 30 samples (33 %) and variant E in 62 samples (69 %). Variants B and C were not detected at all. A statistically significant correlation was observed between the presence of variant E and lymph nodes involvement (p = 0.037) and metastasis (p = 0.041). CONCLUSIONS: With the newly developed tools, the possibility of inclusion of COL11A1 variants as prognostic biomarkers in emerging multiparameter technologies examining tissue RNA expression should be further explored.

Peripheral blood lymphocytes from patients with bipolar disorder demonstrate apoptosis and differential regulation of advanced glycation end products and S100B.

BACKGROUND: This study addresses the expression of the glycosylated proteins known as advanced glycation end products (AGEs), the calcium binding protein S100B and the apoptotic parameters cytochome c and caspase-3 activity in peripheral lymphocyte cytosolic extracts from a sample of bipolar disorder (BD) patients and healthy (control) subjects. METHODS: Cross-sectional study of 35 patients with a clinical diagnosis of bipolar disease (10 euthymic, 12 depressed, 13 manic) and 10 healthy control subjects. Lymphocytes were used as a surrogate model in BD diagnosis and treatment. AGEs and S100B in lymphocyte cell extracts were measured by commercially available enzyme-linked immunosorbent assay. RESULTS: AGEs were lower in all BD patients compared to healthy subjects. Depressed patients had approximately two-fold higher S100B levels compared to healthy subjects. Manic and depressed BD patients had increased superoxide dismutase mRNA levels. Apoptosis as measured by BAX/Bcl2 ratio, cytochrome c release, caspase-3 activity was increased in manic and depressed patients compared to healthy subjects. In the depressed patients, S100B levels correlated with cytochrome c release. CONCLUSIONS: In conclusion, our study shows decreased AGEs and increased S100B levels and caspase down-stream apoptosis in peripheral lymphocytes of BD patients that may underlie disease etiopathogenesis.

Preliminary biomarkers for identification of human ascending thoracic aortic aneurysm.

BACKGROUND: Human ascending thoracic aortic aneurysms (ATAAs) are life threatening and constitute a leading cause of mortality in the United States. Previously, we demonstrated that collagens α2(V) and α1(XI) mRNA and protein expression levels are significantly increased in ATAAs. METHODS AND RESULTS: In this report, the authors extended these preliminary studies using high-throughput proteomic analysis to identify additional biomarkers for use in whole blood real-time RT-PCR analysis to allow for the identification of ATAAs before dissection or rupture. Human ATAA samples were obtained from male and female patients aged 65 ± 14 years. Both bicuspid and tricuspid aortic valve patients were included and compared with nonaneurysmal aortas (mean diameter 2.3 cm). Five biomarkers were identified as being suitable for detection and identification of ATAAs using qRT-PCR analysis of whole blood. Analysis of 41 samples (19 small, 13 medium-sized, and 9 large ATAAs) demonstrated the overexpression of 3 of these transcript biomarkers correctly identified 79.4% of patients with ATAA of ≥4.0 cm (P<0.001, sensitivity 0.79, CI=0.62 to 0.91; specificity 1.00, 95% CI=0.42 to 1.00). CONCLUSION: A preliminary transcript biomarker panel for the identification of ATAAs using whole blood qRT-PCR analysis in men and women is presented.

Effect of postoperative course on midterm outcome after esophageal resection for cancer.

Esophageal resections are challenging procedures often associated with postoperative complications and a prolonged hospital stay. This study investigated the impact of postoperative course on midterm survival in 35 patients undergoing esophageal resection for malignancy between January 2002 and November 2007. The impact of preoperative and operative variables, pathology, staging, early postoperative complications, and length of hospital stay on midterm survival was determined with Cox regression analysis. During the follow-up period, 17 (48.6%) patients died. Multivariate analysis identified surgical stage and length of stay as independent predictors of midterm survival; in addition, the total number of complications reached statistical significance. In conclusion, in addition to surgical stage, postoperative course has an impact upon midterm survival after esophageal resection.

Coronary artery ectasia and inflammatory cytokines: link with a predominant Th-2 immune response?

OBJECTIVE: The role of inflammation in coronary artery ectasia (CAE) remains controversial. We evaluated the hypothesis that CAE might be associated with a specific pattern of T helper (Th) lymphocyte activation by measuring the Th-1 cytokine, interleukin-2 (IL-2) and the Th-2 cytokines, interleukin-4 (IL-4) and interleukin-6 (IL-6) in patients with CAE, obstructive coronary artery disease (CAD) and controls. METHODS: Serum levels of IL-2, IL-4 and IL-6 were measured in 74 patients undergoing an elective cardiac catheterization due to angina pectoris and positive or equivocal non-invasive screening for cardiac ischaemia: 34 had CAE and non-obstructive CAD (Group A), 22 had obstructive CAD (Group B) and 18 had normal coronaries (Group C). RESULTS: Group A had significantly higher IL-4 than Group B and Group C (p<0.001 and p=0.006, respectively). In contrast, Group A had markedly lower IL-2 than Group B and Group C (p<0.001 for both comparisons). Group C had higher IL-4 and lower IL-2 than Group B (p<0.001 for both comparisons). Interleukin-6 was significantly higher in Groups A and B compared to Group C (p<0.001 for both comparisons), whilst it was comparable between Group A and Group B. Multivariate logistic regression analysis showed that higher levels of IL-4 and lower levels of IL-2 were the strongest independent predictors associated with CAE (OR: 3.846, CI: 1.677-8.822, p=0.001 and OR: 0.567, CI: 0.387-0.831, p=0.004, respectively). CONCLUSIONS: Our data demonstrates that Th-2 immune response, exhibited through increased IL-4 and low IL-2, constitutes a fundamental feature of CAE.

Aprikalim a potassium adenosine triphosphate channel opener reduces neurologic injury in a rabbit model of spinal cord ischemia.

BACKGROUND: Potassium adenosine triphosphate (KATP) channel openers have been involved in the enhancement of ischemic tolerance in various tissues. The purpose of the present study is to evaluate the effects of aprikalim, a specific KATP channel opener, on spinal cord ischemic injury. METHODS: Fifty-four rabbits were randomly assigned to three groups: group 1 (n = 18, sham operation), group 2 (n = 18, 30 min of normothermic aortic cross-clamping) and group 3 (n = 18, aprikalim 100 µg/kg was administered 15 min before 30 min of normothermic aortic cross-clamping). Neurologic evaluation was performed according to the modified Tarlov scale. Six animals from each group were sacrificed at 24, 48 and 168 h postoperatively. The lumbar spinal cords were harvested and examined histologically. The motor neurons were counted and the histologic lesions were scored (0-3, 3: normal). RESULTS: Group 3 (aprikalim group) had better Tarlov scores compared to group 2 at all-time points (P < 0.025). The histologic changes were proportional to the Tarlov scores and group 3 had better functional outcome as compared to group 2 at 168 h (number of neurons: 21.2 ± 4.9 vs. 8.0 ± 2.7, P < 0.001 and histologic score: 1.67 ± 1.03 vs. 0.50 ± 0.55, P = 0.03). Although aprikalim exhibited improved effect on clinical and histologic neurologic outcome when compared to normothermic spinal cord ischemia, animals in group 3 had worse Tarlov score, reduced number of motor neurons and worse histologic score when compared to group 1 (sham operation) at 168 h (P = 0.003, P = 0.001 and P = 0.019 respectively). CONCLUSION: Aprikalim reduces the severity of spinal cord ischemic injury in a rabbit model of spinal cord ischemia.

Treatment with simvastatin inhibits the formation of abdominal aortic aneurysms in rabbits.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a common and lethal disease. AAAs are associated with atherosclerosis, chronic inflammation, and extracellular matrix degradation. The aim of this study was to determine whether treatment with simvastatin can influence the development of experimental aortic aneurysms in a rabbit model. MATERIALS AND METHODS: A total of 76 rabbits were randomized in four groups: in group I (n = 12), where the abdominal aortas were exposed to 0.9% NaCl, and in group II (n = 24), group III (n = 24) and group IV (n = 18), where the aortas were exposed to CaCl2 0.5 mol/L for 15 minutes after laparotomy. Group III received 2 mg/kg simvastatin daily starting 7 days before laparotomy, and in group IV, the daily treatment with simvastatin started 7 days after laparotomy. Animals were sacrificed at intervals of first, second, third, and fourth week to obtain measurements of aortic diameter and histological examination. Moreover, immunohistochemistry was used in order to examine the relative distribution of matrix metalloproteinases (MMPs) 2 and 9 (MMP-2 and MMP-9, respectively) and tissue inhibitor 1 of MMPs within the aortic aneurysms. RESULTS: The increase of aortic diameter in animals of group I ranged from 4.6% to 7.6%; in group II, from 41% to 85% (P < 0.001 vs. group I); in group III, from 9% to 18% (group II vs. group III, P < 0.001); and in group IV; from 36% to 38%. Moreover, aortic specimens of group II presented a statistically significant increase in MMP-2 and MMP-9 immunoexpression compared with other groups (I, III, IV) (P < 0.05 for all comparisons), with the exception of animals of group IV at the end of second week. Immunoreactivity of tissue inhibitor 1 of MMPs was not statistically different among groups II, III, and IV. CONCLUSIONS: Simvastatin may prove clinically significant in suppressing the development and expansion of AAAs and, thereby, in reducing the risk of rupture and the need for repair.

Postoperative and long-term outcome of patients with chronic obstructive pulmonary disease undergoing coronary artery bypass grafting.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been conventionally associated with increased operative mortality and morbidity after coronary artery bypass grafting. Some studies, however, challenge this association. Moreover, the effect of COPD on long-term survival after coronary artery bypass grafting has not been adequately assessed. Thus, in this clinical setting, both early and late outcome require further examination. METHODS: We studied 3,760 consecutive patients who underwent isolated coronary artery bypass grafting between 1992 and 2002. The propensity for COPD was determined by logistic regression analysis, and each patient with COPD was matched with 3 patients without COPD. Matched groups were compared for early outcome and long-term survival (mean follow-up, 7.6 years). Long-term survival data were obtained from the National Death Index. RESULTS: There were 550 patients (14.6%) with COPD. Multivariate analysis showed that patients with COPD were older and sicker. However, propensity-matched groups did not differ in terms of hospital mortality or major morbidity, although COPD was associated with a slightly longer hospital stay. In contrast, COPD patients had increased long-term mortality, with a hazard ratio of 1.28 (95% confidence intervals, 1.11 to 1.47; p=0.001). Freedom from all-cause mortality at 7 years after CABG was 65% and 72% in matched patients with and without COPD, respectively (p=0.008). In patients with COPD, the hazard estimate was consistently increased up to 9 years postoperatively. CONCLUSIONS: Chronic obstructive pulmonary disease, although not an independent predictor of increased early mortality and morbidity in this series, is a continuing detrimental risk factor for long-term survival.